Colorectal cancer is a major public health problem in the United States and worldwide, with more than 150,000 new cases expected to be diagnosed in 2007 and more than 52,000 individuals expected to die from their disease. A multitude of factors may contribute to prognosis, including tumor characteristics, patient genetics, and lifestyle factors. Cancer survivors are faced with many difficult decisions, including what they can do to improve their chances of survival and well-being. Unfortunately, we are far from making science-based recommendations. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly available and are effective chemopreventive agents against colorectal carcinogenesis. However, it is currently unknown whether they are similarly beneficial for use among cancer survivors. The goal of this research is to examine whether the advantages of NSAIDs in reducing colorectal cancer incidence extend to reducing mortality, particularly in subsets defined by genetic susceptibility. Specifically we will 1) examine among colorectal cases with local/regional disease whether prognosis is related to NSAID use, evaluated prior to diagnosis, and 2) determine if NSAID-related genotypes are related to survival. As a secondary aim, we plan to explore whether associations with genetic factors differ by NSAID use (gene-NSAID interaction). To accomplish these aims we will analyze data from the Seattle Colorectal Cancer Family Registry (CCFR), a site in the multi-centered international NIH-funded Colorectal Cancer Family Registry. Eligible cases will be from this population based on cases of colorectal cancer enrolled from 1998-2002 (n=1560). All cases completed a standardized assessment of NSAID use, including type, recency, and duration, as well as other known and suspected risk factors for colorectal cancer. Genotyping of polymorphisms in genetic polymorphisms in NSAID metabolism and prostaglandin synthesis (n=1268) is currently getting completed under separate funding. Follow up for vital status, and cause of death using data linkages will be completed for all cases and will include a median 7.5 years of follow-up. The proposed study will address critical questions of colorectal cancer prognosis and the Seattle CCFR is uniquely suited for this research, because of its large number of population-based colorectal cancer cases, the high prevalence of NSAID use, biospecimens and clinical data collected, and genotyping underway. Thus, the proposed study will be highly cost-effective. Results from this study will yield potentially important information for cancer patients and clinicians. It will also provide important insights into the biology of this common cancer.